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Treatment of hypertension in asthma and COPD

Treatment of hypertension in asthma and COPD
Literature review current through: Jan 2024.
This topic last updated: May 17, 2022.

INTRODUCTION — The management of hypertension in a patient with asthma or chronic obstructive pulmonary disease (COPD) is a common problem owing to the high prevalence of each condition in the adult population. Indications for treatment of hypertension and use of nonpharmacologic approaches are similar in patients with or without either of these conditions. (See "Overview of hypertension in adults".)

OVERVIEW — Pharmacologic treatment of hypertension in patients with asthma or COPD may be complicated by the asthma-exacerbating effect of some antihypertensives. As an example, beta blockers should be used with great caution or not at all in patients with chronic asthma (but not COPD), acute allergic or exercise-induced bronchospasm, or asthma-COPD overlap syndrome. The angiotensin-converting enzyme (ACE) inhibitors, among the most widely used antihypertensive drugs, are not contraindicated in asthma or COPD, but they can induce a bothersome cough that, although not damaging to the lungs, can be confused with cough due to underlying pulmonary diseases such as asthma and COPD.

Beta blockers — Beta blockers can increase airway reactivity and may interfere with the activity of beta-agonists. However, beta blockers are safe for use in most patients with COPD, but less so in patients with asthma.

COPD — Beta blockers, particularly beta-1 selective beta blockers (table 1), appear to be safe in most patients with COPD.

In some observational studies of patients with COPD, beta blocker (including beta-1 selective and nonselective) use was associated with a reduction in mortality and exacerbations of respiratory symptoms [1,2]. In addition, in a meta-analysis including 10 trials of patients with COPD, short-term selective beta-blocker therapy did not change baseline forced expiratory volume in the first second (FEV1) or increase respiratory symptoms [3].

However, in a subsequent trial including patients with moderate to severe COPD and no primary cardiovascular indication for beta blockers, metoprolol increased the risk of hospitalization for COPD exacerbations (HR 1.91, 95% CI 1.29-2.83), although the overall rate of COPD exacerbations was not increased [4]. However, in the Rotterdam Study, an observational study including over 1300 participants with COPD, cardioselective beta blockers were associated with a reduced risk of COPD exacerbations only among those who had a cardiovascular indication for use of a beta blocker, but not in those without a cardiovascular indication [5]. (See "Management of the patient with COPD and cardiovascular disease", section on 'Effect of cardioselective beta blockers on lung function'.)

Asthma — In patients with asthma, beta blockers can cause increased bronchial obstruction and airway reactivity, as well as resistance to the effects of inhaled or oral beta receptor agonists (such as albuterol or terbutaline) [6-8]. Even topical ophthalmic administration of nonselective beta blockers for the treatment of glaucoma has led to asthmatic exacerbations [9]. Although the precise mechanism of beta blocker-induced bronchoconstriction is unknown, parasympathetic pathways of airway control may be involved since the anticholinergic drug oxitropium bromide can inhibit the effect of inhaled propranolol [10].

Although beta-1 selective blockers are safer than nonselective beta blockers (table 1), they should still be used with caution in patients with asthma, particularly in those with severe obstruction or markedly reduced pulmonary function at baseline [11]. As an example, in a meta-analysis of 32 randomized trials including over 1300 patients with asthma, nonselective beta blockers caused a greater reduction in FEV1 compared with beta-1 selective beta blockers (by 10 versus 7 percent), and also attenuated the response to inhaled beta agonists compared with beta-1 selective blockers (by 20 versus 10 percent) [6]. However, one in eight patients on beta-1 selective blockers had a 20 percent or larger decrease in FEV1.

ACE inhibitors — ACE inhibitors are not first-line therapy in patients with COPD or asthma. They increase the likelihood of cough (which may be confused with an exacerbation of COPD or asthma) and, in patients with asthma, they may worsen airflow obstruction (although this is uncommon). However, their use is not contraindicated in such patients.

The most common side effect of therapy with angiotensin-converting enzyme (ACE) inhibitors is cough (typically described as dry, irritative, and persistent, but rarely productive), which develops in 3 to 20 percent of patients [12]. When this cough develops in a patient with either asthma or COPD, it can be confused with an increase in symptoms related to underlying airway disease. There are conflicting data on whether patients with underlying asthma are more likely than non-asthmatics to develop cough after ACE inhibition [12,13].

There is no evidence of adverse effects of ACE inhibitors on the course of COPD [14]. However, in asthmatic patients, some cases of worsening asthma with ACE inhibitors have been described. In one study examining adverse respiratory effects to ACE inhibitors, reactions diagnosed as asthma, bronchospasm, or dyspnea were reported at one-tenth the frequency of cough, with several cases of bronchospasm occurring in patients with known asthma [15]. In addition, the possibility that ACE inhibitor cough may represent an asthma equivalent has been suggested by the demonstration of bronchial hyperresponsiveness in some, but not all, affected patients [16,17]. (See "Major side effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers", section on 'Cough'.)

An alternative, when it is desirable to block the renin-angiotensin system, is administration of an angiotensin II receptor blocker. (See "Renin-angiotensin system inhibition in the treatment of hypertension" and 'Angiotensin receptor blockers' below.)

Angiotensin receptor blockers — Angiotensin II receptor blockers (ARBs) do not appear to induce cough, and may be used safely in patients with asthma or chronic obstructive pulmonary disease (COPD). In one small trial including hypertensive patients with asthma, there was no increase in cough or bronchial hyperreactivity with an ARB, and it was as well tolerated as calcium channel blockers [18].

Diuretics — Thiazide diuretics are generally safe to use among patients with chronic obstructive pulmonary disease (COPD) [19].

However, there may be potential issues related to metabolic alkalosis and, among those also using beta agonists or glucocorticoids, hypokalemia:

Among patients with COPD and chronic hypercapnia, diuretics can also induce a metabolic alkalosis, which can suppress the ventilatory drive and potentially exacerbate hypoxemia [20,21].

Inhaled beta agonists can drive potassium into the cells, acutely lowering the plasma potassium concentration by as much as 0.5 to 1 mEq/L [22]. Glucocorticoids may lower serum potassium by mildly enhancing urinary potassium excretion [22,23]. Thiazide diuretics also reduce the serum potassium, and therefore concomitant use of these agents with beta agonists or glucocorticoids can exacerbate hypokalemia [21]. (See "Causes of hypokalemia in adults".)

Thus, it is safest to administer only low thiazide doses (eg, 12.5 to 25 mg of hydrochlorothiazide once daily) to nonedematous hypertensive patients with asthma or COPD. Low-dose therapy may be effective and less likely to produce unwanted side effects such as metabolic alkalosis and hypokalemia. (See "Use of thiazide diuretics in patients with primary (essential) hypertension".)

Calcium channel blockers — The calcium channel blockers (especially those of the dihydropyridine group, such as nifedipine and nicardipine) are excellent agents for the treatment of hypertension in asthma [21,24]. (See "Major side effects and safety of calcium channel blockers".)

In addition to effectively lowering the blood pressure, calcium channel blockers also have the theoretical advantages of opposing muscle contraction in tracheobronchial smooth muscle, inhibiting mast cell degranulation, and possibly reinforcing the bronchodilator effect of beta agonists. Nifedipine, for example, can antagonize the bronchoconstricting effects of antigen, histamine, or cold air challenge [25]. Although some studies have shown a mild improvement in airway function [25], most studies have demonstrated no effect of calcium antagonists on asthma [26,27] .

Sympathetic blockers — Clonidine and other alpha-2 receptor agonists (methyldopa, guanabenz) should be used with caution in asthmatics. Oral doses of these agents do not change baseline air flow in asthmatics, but they do increase bronchial reactivity to inhaled histamine [28].

Other — Little specific information is available for the remaining antihypertensive agents, such as hydralazine. However, if asthma occurs with these or other drugs, one should always consider the possibility that the tartrazine dye within the drug preparation may be the culprit.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Hypertension in adults".)

SUMMARY

Overview – Indications for treatment of hypertension and use of nonpharmacologic approaches are similar in patients with or without asthma or chronic obstructive pulmonary disease (COPD). The management of hypertension in a patient with either of these conditions may be made difficult by the asthma-exacerbating effect of some antihypertensive drugs. (See 'Introduction' above and 'Overview' above.)

Beta blockers – Beta blockers can cause increased bronchial obstruction and airway reactivity, as well as resistance to the effects of inhaled or oral beta receptor agonists (such as albuterol or terbutaline) in patients with asthma but not COPD. Although the clinical effects of more beta-1-selective beta blockers on pulmonary function appear to be less severe, even beta-1-selective agents should be used with caution in asthmatic patients with severe obstruction or markedly reduced baseline pulmonary function (table 1). (See 'Beta blockers' above.)

ACE inhibitors and angiotensin receptor blockers – Angiotensin-converting enzyme (ACE) inhibitors are not first-line therapy in patients with COPD or asthma. They increase the likelihood of cough (which may be confused with an exacerbation of COPD or asthma) and, in patients with asthma, they may worsen airflow obstruction (although this is uncommon). However, their use is not contraindicated in such patients. An alternative, when it is desirable to block the renin-angiotensin system, is administration of an angiotensin II receptor blocker. (See 'ACE inhibitors' above and 'Angiotensin receptor blockers' above.)

Diuretics – Diuretics can be effectively used in asthmatics but may cause serious hypokalemia if used concurrently with inhaled beta-2 receptor agonists, which drive potassium into the cells, and oral corticosteroids, which enhance urinary potassium excretion. In addition, diuretic-induced metabolic alkalosis can suppress ventilatory drive, potentially exacerbating the degree of hypoxemia. It is safest to administer only low thiazide doses (12.5 to 25 mg of hydrochlorothiazide once daily) to nonedematous hypertensive patients with asthma or COPD. (See 'Diuretics' above.)

Calcium channel blockers – The calcium channel blockers (especially those of the dihydropyridine group, such as nifedipine and nicardipine) are excellent agents for the treatment of hypertension in asthma. In addition to effectively lowering the blood pressure, they also have the theoretical advantages of opposing muscle contraction in tracheobronchial smooth muscle, inhibiting mast cell degranulation, and possibly reinforcing the bronchodilator effect of beta agonists. (See 'Calcium channel blockers' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Norman Kaplan, MD, who contributed to an earlier version of this topic review.

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